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. 2018 Jul 2;15(7):2606-2613.
doi: 10.1021/acs.molpharmaceut.8b00133. Epub 2018 May 30.

86/90Y-Based Theranostics Targeting Angiogenesis in a Murine Breast Cancer Model

Emily B Ehlerding, Carolina A Ferreira  1 , Eduardo Aluicio-Sarduy, Dawei Jiang, Hye Jin Lee, Charles P Theuer  2 , Jonathan W Engle, Weibo Cai  1   3
Affiliations

86/90Y-Based Theranostics Targeting Angiogenesis in a Murine Breast Cancer Model

Emily B Ehlerding et al. Mol Pharm. .

Abstract

Angiogenesis is widely recognized as one of the hallmarks of cancer. Therefore, imaging and therapeutic agents targeted to angiogenic vessels may be widely applicable in many types of cancer. To this end, the theranostic isotope pair, 86Y and 90Y, were used to create a pair of agents for targeted imaging and therapy of neovasculature in murine breast cancer models using a chimeric anti-CD105 antibody, TRC105. Serial positron emission tomography imaging with 86Y-DTPA-TRC105 demonstrated high uptake in 4T1 tumors, peaking at 9.6 ± 0.3%ID/g, verified through ex vivo studies. Additionally, promising results were obtained in therapeutic studies with 90Y-DTPA-TRC105, wherein significantly ( p < 0.05) decreased tumor volumes were observed for the targeted treatment group over all control groups near the end of the study. Dosimetric extrapolation and tissue histological analysis corroborated trends found in vivo. Overall, this study demonstrated the potential of the pair 86/90Y for theranostics, enabling personalized treatments for cancer.

Keywords: CD105/endoglin; angiogenesis; cancer; positron emission tomography (PET); radioimmunotherapy; theranostics; yttrium-86; yttrium-90.

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Conflict of interest statement

Notes

The authors declare the following competing financial interest(s): C.P.T. is an employee of TRACON Pharmaceuticals, Inc. The other authors declare no competing financial interests.

Figures

Figure 1
Figure 1
PET imaging of 86Y-DTPA-TRC105. (A) Serial representative PET MIP images reveal prominent uptake in the 4T1 tumor, indicated by a red arrow. (B) ROI analysis of blood pool and tumor uptake. (C) Ex vivo biodistribution of 86Y-DTPA-TRC105 at 48 h postinjection, n = 4.
Figure 2
Figure 2
Results of the therapeutic study. (A) Average (±SD) tumor volumes for all groups over the 14 day study. (B) Kaplan–Meier survival curve. *p < 0.05 for 90Y-DTPA-TRC105 group as compared to all others, n = 5–6 per group.
Figure 3
Figure 3
Serial Cherenkov imaging. Tumors are indicated by red arrows.
Figure 4
Figure 4
Immunofluorescent and H&E staining of tumor tissues. Colocalization of CD31 and CD105, indicated by yellow arrows, shows angiogenic vessels. H&E staining visualized notable damage to 90Y-treated tumors, with red arrows pointing out representative damaged areas, and blue arrows indicating hemorrhaging.
Figure 5
Figure 5
Dosimetric evaluation of 90Y-DTPA-TRC105. (A) Doses to off-target organs. (B) Dose-to-sphere modeling of tumors of various sizes. N = 4.
See this image and copyright information in PMC

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